P356: SUBGROUP ANALYSES OF KTE-X19, AN ANTI-CD19 CHIMERIC ANTIGEN RECEPTOR (CAR) T-CELL THERAPY, IN ADULT PATIENTS WITH RELAPSED OR REFRACTORY B-CELL ACUTE LYMPHOBLASTIC LEUKEMIA (R/R B-ALL) IN ZUMA-3
Authors: B. D. Shah, R. D. Cassaday, J. H. Park, R. Houot, O. O. Oluwole, A. C. Logan, N. Boissel, T. Leguay, M. R. Bishop, M. S. Topp, D. Tzachanis, K. M. O’Dwyer, M. L. Arellano, Y. Lin, M. R. Baer, G. J. Schiller, M. Subklewe, M. Abedi, M. C. Minnema, W. G. Wierda, D. J. DeAngelo, P. Stiff, D. Jeyakumar, J. Dong, S. Adhikary, L. Zhou, P. C. Schuberth, B. Kharabi Masouleh, A. Ghobadi
Journal: HemaSphere (2022)

Background: Brexucabtagene autoleucel (KTE-X19) is approved in the US for the treatment of adult patients with R/R B-ALL based on the positive results of the ZUMA-3 study. In the pivotal Phase 2 portion of ZUMA-3, the overall complete remission (CR) rate (CR + CR with incomplete hematologic recovery [CRi]) was 71% (N=55; median follow-up 16.4 months; Shah et al. Lancet 2021). Aims: To assess outcomes in ZUMA-3 by prior number of therapy lines, prior blinatumomab, prior allogeneic stem cell transplant (alloSCT), and subsequent alloSCT. Methods: Eligible adults had R/R B-ALL and received a single infusion of KTE-X19 following leukapheresis and conditioning chemotherapy. Outcomes assessed by independent review are reported in all patients treated at the pivotal dose (1×106 CAR T cells/kg). Results: As of 23 July 2021, the median follow-up among all treated patients in Phase 2 (N=55) was 26.8 months (range, 20.7-32.6). At baseline, 10 patients (18%) had 1 prior line of therapy, and 45 patients (82%) had ≥2 prior lines. The overall CR/CRi rates (95% CI) for patients with 1 or ≥2 prior lines of therapy were 90% (55-100) and 67% (51-80), respectively. In patients with 1 or ≥2 prior lines of therapy, the median (95% CI) duration of remission (DOR) was 4.7 months (1.8-not estimable [NE]) and 14.6 months (9.4-NE), and the median (95% CI) overall survival (OS) was not reached (NR) (2.1-NE) and 25.4 months (14.2-NE), respectively. Grade ≥3 cytokine release syndrome (CRS) occurred in 10% and 27% of patients with 1 or ≥2 prior lines of therapy, and Grade ≥3 neurologic events occurred in 30% and 24%, respectively. Among the 25 patients (45%) who had prior blinatumomab at baseline, the overall CR/CRi rate (95% CI) was 60% (39-79), and 80% (61-92) in the 30 patients (55%) without prior blinatumomab. The median (95% CI) DOR was 19.1 months (1.3-NE) and 10.3 months (5.2-NE) in patients with or without prior blinatumomab, and the median (95% CI) OS was 14.2 months (3.2-26.0) and NR (18.6-NE), respectively. In patients with or without prior blinatumomab, rates of Grade ≥3 CRS were 24% and 23%, and rates of Grade ≥3 neurologic events were 20% and 30%, respectively. The overall CR/CRi rate in the 23 patients (42%) who had prior alloSCT vs the 32 patients (58%) who did not was 70% (47-87) vs 72% (53-86), respectively. In patients with vs without prior alloSCT, the medians (95% CI) for DOR were 14.6 months (8.7-23.6) vs NR (4.7-NE), and the medians (95% CI) for OS were 25.4 months (14.2-NE) vs NR (9.0-NE), respectively. Grade ≥3 CRS occurred in 17% and 28% of patients with or without prior alloSCT, and Grade ≥3 neurologic events occurred in 26% and 25%, respectively. For patients who achieved CR/CRi and did (n=10) or did not (n=29) proceed to subsequent alloSCT post–KTE-X19 infusion, the median (95%CI) DOR was NR (NE-NE) and 14.6 months (8.7-23.6), and the median (95% CI) OS was NR (7.6-NE) and 26.0 months (18.6-NE), respectively. A pooled analysis of all Phase 1 and 2 patients treated at the pivotal dose (N=78) was newly conducted, with a median follow-up of 29.7 months (range, 20.7-58.3). The similar results observed in this expanded data set as shown in the Table further support the subgroup outcomes described above in Phase 2 patients. Image:Summary/Conclusion: Adults with R/R B-ALL benefitted from KTE-X19, with manageable safety, regardless of prior exposure to blinatumomab or prior alloSCT, though survival appeared better in patients without these prior therapies and in earlier lines of therapy, with limited patient numbers in some subgroups. roups.